Altered olfactory function in the MRL model of CNS lupus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that damages several bodily systems, including the CNS. Brain atrophy and diverse neuropsychiatric manifestations are common and serious complications of SLE. Recently, it has been reported that many patients with CNS involvement also present with olfactory deficits of unknown etiology. Similar to CNS SLE, spontaneous development of lupus-like disease in MRL/lpr mice is accompanied by neurodegeneration in periventricular regions and a constellation of behavioral deficits dependent on olfaction. To test the possibility that olfactory dysfunction also occurs in autoimmune mice, we presently examine odor-guided behaviors using a battery of paradigms. Indeed, lupus-prone males spent less time exploring unfamiliar conspecifics and demonstrated age-dependant performance deficits when exposed to low concentrations of attractant and repellant odors. The emergence of olfactory changes was associated with a skewed distribution of DCX+ cells in the proximal portion of the rostral migratory stream (RMS). The present results are consistent with the hypothesis that the onset of a SLE-like condition affects periventricular regions, including the RMS, as evidenced by disrupted migration of neuronal precursor cells toward the olfactory bulb. If so, ensuing hyposmia and/or olfactory memory deficit may contribute to altered performance in other behavioral tasks and reflect a prodrome of brain damage induced by chronic autoimmune disease.

► Lupus-like disease is associated with altered response to low-concentrated odors.
► Behavioral changes are accompanied by altered distribution of neuroblasts in the RMS.
► Changes in olfactory sensitivity may affect performance in odor-guided behavioral tasks.